Prognostic value of computed tomography radiomics features in patients with gastric neuroendocrine neoplasm.

Purpose: The present study aimed to investigate the clinical prognostic significance of radiomics signature (R-signature) in patients with gastric neuroendocrine neoplasm (GNEN). Methods and Materials: A retrospective study of 182 patients with GNEN who underwent dual-phase enhanced computed tomography (CT) scanning was conducted. LASSO-Cox regression analysis was used to screen the features and establish the arterial, venous and the arteriovenous phase combined R-signature, respectively. The association between the optimal R-signature with the best prognostic performance and overall survival (OS) was assessed in the training cohort and verified in the validation cohort. Univariate and multivariate Cox regression analysis were used to identify the significant factors of clinicopathological characteristics for OS. Furthermore, the performance of a combined radiomics-clinical nomogram integrating the R-signature and independent clinicopathological risk factors was evaluated. Results: The arteriovenous phase combined R-signature had the best performance in predicting OS, and its C-index value was better than the independent arterial and venous phase R-signature (0.803 vs 0.784 and 0.803 vs 0.756, P<0.001, respectively). The optimal R-signature was significantly associated with OS in the training cohort and validation cohort. GNEN patients could be successfully divided into high and low prognostic risk groups with radiomics score median. The combined radiomics-clinical nomogram combining this R-signature and independent clinicopathological risk factors (sex, age, treatment methods, T stage, N stage, M stage, tumor boundary, Ki67, CD56) exhibited significant prognostic superiority over clinical nomogram, R-signature alone, and traditional TNM staging system (C-index, 0.882 vs 0.861, 882 vs 0.803, and 0.882 vs 0.870 respectively, P<0.001). All calibration curves showed remarkable consistency between predicted and actual survival, and decision curve analysis verified the usefulness of the combined radiomics-clinical nomogram for clinical practice. Conclusions: The R-signature could be used to stratify patients with GNEN into high and low risk groups. Furthermore, the combined radiomics-clinical nomogram provided better predictive accuracy than other predictive models and might aid clinicians with therapeutic decision-making and patient counseling.

Application of computed tomography-based radiomics in differential diagnosis of adenocarcinoma and squamous cell carcinoma at the esophagogastric junction.

BACKGROUND: The biological behavior of carcinoma of the esophagogastric junction (CEGJ) is different from that of gastric or esophageal cancer. Differentiating squamous cell carcinoma of the esophagogastric junction (SCCEG) from adenocarcinoma of the esophagogastric junction (AEG) can indicate Siewert stage and whether the surgical route for patients with CEGJ is transthoracic or transabdominal, as well as aid in determining the extent of lymph node dissection. With the development of neoadjuvant therapy, preoperative determination of pathological type can help in the selection of neoadjuvant radiotherapy and chemotherapy regimens. AIM: To establish and evaluate computed tomography (CT)-based multiscale and multiphase radiomics models to distinguish SCCEG and AEG preoperatively. METHODS: We retrospectively analyzed the preoperative contrasted-enhanced CT imaging data of single-center patients with pathologically confirmed SCCEG (n = 130) and AEG (n = 130). The data were divided into either a training (n = 182) or a test group (n = 78) at a ratio of 7:3. A total of 1409 radiomics features were separately extracted from two dimensional (2D) or three dimensional (3D) regions of interest in arterial and venous phases. Intra-/inter-observer consistency analysis, correlation analysis, univariate analysis, least absolute shrinkage and selection operator regression, and backward stepwise logical regression were applied for feature selection. Totally, six logistic regression models were established based on 2D and 3D multi-phase features. The receiver operating characteristic curve analysis, the continuous net reclassification improvement (NRI), and the integrated discrimination improvement (IDI) were used for assessing model discrimination performance. Calibration and decision curves were used to assess the calibration and clinical usefulness of the model, respectively. RESULTS: The 2D-venous model (5 features, AUC: 0.849) performed better than 2D-arterial (5 features, AUC: 0.808). The 2D-arterial-venous combined model could further enhance the performance (AUC: 0.869). The 3D-venous model (7 features, AUC: 0.877) performed better than 3D-arterial (10 features, AUC: 0.876). And the 3D-arterial-venous combined model (AUC: 0.904) outperformed other single-phase-based models. The venous model showed a positive improvement compared with the arterial model (NRI > 0, IDI > 0), and the 3D-venous and combined models showed a significant positive improvement compared with the 2D-venous and combined models (P < 0.05). Decision curve analysis showed that combined 3D-arterial-venous model and 3D-venous model had a higher net clinical benefit within the same threshold probability range in the test group. CONCLUSION: The combined arterial-venous CT radiomics model based on 3D segmentation can improve the performance in differentiating EGJ squamous cell carcinoma from adenocarcinoma.

Extranodal nasal NK/T cell lymphoma with bronchial mucoepidermoid carcinoma and lung adenocarcinoma: a case report.

Extranodal nasal NK/Tcell lymphoma (ENKTCL) is a relatively rare type of non-Hodgkin's lymphoma. It is highly malignant, highly invasive, and easy to relapse. Most patients have a poor prognosis. We report a 48-year-old woman who presented with irritant dry cough that had persisted for 6 m. CT showed a mass in the right nasal cavity, with uneven density similar to soft tissue, with slight uneven enhancement. The mass and the upper, middle, and lower turbinates were not clearly demarcated, involving multiple adjacent sinus cavities, and the local bone showed osteolytic destruction; MRI showed isosignal on T1WI and slightly hypersignal on T2WI and DWI. In addition, there was a mass of soft tissue density at the bronchial opening in the right middle lobe, showing uneven and obvious enhancement; a cavity was seen in the nodule of the right lower lobe, and the adjacent pleura was stretched, showing moderate enhancement. The nasal mass was diagnosed as extranodal NK/T cell lymphoma, the right middle lobe mass was diagnosed as mucoepidermoid carcinoma, and the right lower lobe mass was diagnosed as lung adenocarcinoma. ENKTCL rarely invades the lungs. If a patient has a lung occupying lesion similar to it, biopsy confirmation should be considered to avoid misdiagnosis as a chest metastasis that affects the treatment effect.

Computed Tomography Features and Clinical Prognostic Characteristics of Hepatoid Adenocarcinoma of the Stomach.

PURPOSE: Hepatoid adenocarcinoma of the stomach (HAS) is a highly malignant and aggressive tumor. The purpose of this study was to describe the clinical, computed tomography (CT), and prognostic features of HAS to increase the awareness of this entity and determine its distinguishing features from non-HAS tumors. METHODS: The CT features and clinical data of 47 patients in our hospital with pathologically documented HAS were retrospectively analyzed, and the relevant differences between pure HAS (pHAS) and mixed HAS (mHAS) were determined. In addition, 141 patients with non-HAS tumors in the same T stage in the same period were selected as the control group. The data were compared between the two groups, and factors affecting the prognosis of HAS were analyzed. In addition, we included 9 patients with HAS and 27 patients with non-HAS tumors from another center for external validation. RESULTS: The patients in the HAS group were predominantly men (n = 33), and the tumor location was mostly the cardia or fundus (n = 27). Between the HAS and non-HAS groups, there were observed differences in terms of: sex, serum alpha-fetoprotein (AFP), carbohydrate antigen (CA)-125, and CA-724 levels; longest tumor diameter; degree of differentiation; vascular invasion; N stage, M stage, and tumor-node-metastasis (TNM) stage; thickest tumor diameter; plain CT attenuation; arterial-phase CT attenuation; CT attenuation between the venous and arterial phases; enhancement modes; and degrees of enhancement (all P < 0.05). In the data from another center for external validation, there were observed differences in terms of: age, degree of differentiation, vascular invasion, thickest tumor diameter, the ratio of arterial CT attenuation to CT attenuation of the abdominal aorta at the same level (RA), CT attenuation difference between the venous phase and arterial phase (HUv-a) (all P < 0.05). The results of the multivariate analysis revealed that the independent factors for differentiation were serum AFP level (P = 0.001), M stage (P = 0.038), and tumor enhancement on CT (P = 0.014). Among patients in the HAS group, 72.34% had pHAS and 27.66% had mHAS. The thickest tumor diameter and the longest short diameter of the metastatic lymph nodes of the mHAS group were on average 6.39 cm and 1.45 cm, respectively, which were larger than those in the pHAS group. The median progression-free survival time was 18.25 months in the HAS group, which was shorter than that in the non-HAS group (72.96 months; P = 0.001). The median overall survival time in the HAS group was 24.80 months, which was shorter than that in the non-HAS group (67.96 months; P = 0.001). The factors affecting the prognosis of HAS were M stage (P = 0.001), overall TNM stage (P = 0.048), presence of vascular cancer emboli (P = 0.040), and pHAS type (P = 0.046). Multifactorial analysis revealed that M stage (P = 0.027) and pHAS type (P = 0.009) were independent risk factors affecting the prognosis of HAS. CONCLUSION: Although HAS is a rare clinical entity, it should be considered in the differential diagnosis of gastric tumors. Patients with HAS often have advanced-stage disease at presentation and a worse prognosis than patients with non-HAS tumors. CT findings, combined with laboratory results, can support the diagnosis of HAS. However, the final diagnosis needs to be confirmed with a histopathologic examination. If the postoperative pathologic findings reveal the mHAS type, a rapid clinical intervention and a detailed follow-up with CT are essential.

Development of CT-Based Imaging Signature for Preoperative Prediction of Invasive Behavior in Pancreatic Solid Pseudopapillary Neoplasm.

PURPOSE: It is challenging for traditional CT signs to predict invasiveness of pancreatic solid pseudopapillary neoplasm (pSPN). We aim to develop and evaluate CT-based radiomics signature to preoperatively predict invasive behavior in pSPN. METHODS: Eighty-five patients who had pathologically confirmed pSPN and preoperative contrasted-enhanced CT imaging in our hospital were retrospectively analyzed (invasive: 24; non-invasive: 61). 1316 radiomics features were separately extracted from delineated 2D or 3D ROIs in arterial and venous phases. 200% (SMOTE) was used to generate balanced dataset (invasive: 72, non-invasive: 96) for each phase, which was for feature selection and modeling. The model was internally validated in the original dataset. Inter-observer consistency analysis, spearman correlation, univariate analysis, LASSO regression and backward stepwise logical regression were mainly applied to screen the features, and 6 logistic regression models were established based on multi-phase features from 2D or 3D segmentations. The ROC analysis and Delong's test were mainly used for model assessment and AUC comparison. RESULTS: It retained 11, 8, 7 and 7 features to construct 3D-arterial, 3D-venous, 2D-arterial and 2D-venous model. Based on 3D ROIs, the arterial model (AUC: 0.914) performed better than venous (AUC: 0.815) and the arterial-venous combined model was slightly improved (AUC: 0.918). Based on 2D ROIs, the arterial model (AUC: 0.814) performed better than venous (AUC:0.768), while the arterial-venous combined model (AUC:0.893) performed better than any single-phase model. In addition, the 3D arterial model performed better than the best combined 2D model. The Delong's test showed that the significant difference of model AUC existed in arterial models in original dataset (p = 0.019) while not in arterial-venous combined model (p=0.49) as comparing 2D and 3D ROIs. CONCLUSION: The arterial radiomics model constructed by 3D-ROI feature is potential to predict the invasiveness of pSPN preoperatively.

Lifestyle interventions for patients with nonalcoholic fatty liver disease: a network meta-analysis.

Lifestyle interventions remain the first-line therapy for nonalcoholic fatty liver disease (NAFLD). This study aims to evaluate the individual impact of exercise and/or dietary interventions on the level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), homeostasis model of assessment for insulin resistance index (HOMA-IR), and BMI. Randomized-controlled trials from patients diagnosed with NAFLD were included in the meta-analysis if they reported the associations between changes in ALT, AST, HOMA-IR, or BMI and types of lifestyle interventions. Nineteen eligible articles were included. Compared with observation, aerobic exercise training (AEx) plus diet [weighted mean difference (WMD)=-25.85; 95% confidence interval (CI): -43.90 to -7.80], AEx (WMD=-8.81; 95% CI: -20.22-2.60) and diet (WMD=-11.85; 95% CI: -47.65-24.95) showed significant efficacy in the improvement of ALT levels. Also AST, AEx plus diet showed a significant tendency to reduce AST levels. In addition, progressive resistance training (WMD=-1.70; 95% CI: -5.61-2.21) led to the most obvious reduction in HOMA-IR compared with observation, but appeared to show no significant effect in BMI (WMD=0.27; 95% CI: -0.48 to -0.07), whereas AEx plus diet (WMD=-0.96; 95% CI: -1.54 to -0.38 and WMD=-1.96; 95% CI: -2.79 to -1.12) showed great efficacy both in the improvement of HOMA-IR and BMI. AEx plus diet is the most effective intervention in the management of patients with NAFLD. Dietary intervention may be more effective in the improvements of aminotransferases, whereas exercise shows superiority in improving insulin sensitivity and reduction of BMI.

Development of a prognostic nomogram for cirrhotic patients with upper gastrointestinal bleeding.

BACKGROUND AND AIM: Upper gastrointestinal bleeding (UGIB) is a complication with a high mortality rate in critically ill patients presenting with cirrhosis. Today, there exist few accurate scoring models specifically designed for mortality risk assessment in critically ill cirrhotic patients with upper gastrointestinal bleeding (CICGIB). Our aim was to develop and evaluate a novel nomogram-based model specific for CICGIB. PATIENTS AND METHODS: Overall, 540 consecutive CICGIB patients were enrolled. On the basis of Cox regression analyses, the nomogram was constructed to estimate the probability of 30-day, 90-day, 270-day, and 1-year survival. An upper gastrointestinal bleeding-chronic liver failure-sequential organ failure assessment (UGIB-CLIF-SOFA) score was derived from the nomogram. Performance assessment and internal validation of the model were performed using Harrell's concordance index (C-index), calibration plot, and bootstrap sample procedures. UGIB-CLIF-SOFA was also compared with other prognostic models, such as CLIF-SOFA and model for end-stage liver disease, using C-indices. RESULTS: Eight independent factors derived from Cox analysis (including bilirubin, creatinine, international normalized ratio, sodium, albumin, mean artery pressure, vasopressin used, and hematocrit decrease>10%) were assembled into the nomogram and the UGIB-CLIF-SOFA score. The calibration plots showed optimal agreement between nomogram prediction and actual observation. The C-index of the nomogram using bootstrap (0.729; 95% confidence interval: 0.689-0.766) was higher than that of the other models for predicting survival of CICGIB. CONCLUSION: We have developed and internally validated a novel nomogram and an easy-to-use scoring system that accurately predicts the mortality probability of CICGIB on the basis of eight easy-to-obtain parameters. External validation is now warranted in future clinical studies.

Comparative efficacy of vasoconstrictor therapies for type 1 hepatorenal syndrome: a network meta-analysis.

INTRODUCTION: The outcome of a comparative efficacy and safety of vasoconstrictor therapies for treatment of patients with type 1 hepatorenal syndrome (HRS-1) remain inconclusive. Areas covered: We searched literature databases for randomized controlled trials (RCTs) until 31 January 2016, and included ten eligible RCTs. In conclusion, terlipressin was the most efficacious vasoconstrictor drug for HRS-1, but had a higher probability of causing AEs. Norepinephrine was an attractive alternative to terlipressin and associated with less AEs. Expert commentary: To date, most previous traditional meta-analyses included trials with a limited population and compared terlipressin alone or with albumin against no intervention or albumin. Since different HRS types have different diagnoses and show different responses to vasoconstrictors, it may be questionable to combine data from patients with type 1 and type 2 HRS, which has been reported for most previous meta-analyses. Thus, performing a high-quality network meta-analysis of the existing literature is a valuable way to interrogate published data and to draw conclusions which may inform on the best interventional strategy.

Luteolin reduces obesity-associated insulin resistance in mice by activating AMPKα1 signalling in adipose tissue macrophages.

AIMS/HYPOTHESIS: Inflammatory polarisation of adipose tissue macrophages (ATMs) plays a critical role in the development of obesity-associated metabolic diseases such as insulin resistance and diabetes. Our previous study indicated that dietary luteolin (LU) could prevent the establishment of insulin resistance in mice fed a high-fat diet (HFD). Here, we further investigated the effects of LU, which is a natural flavonoid, on pre-established insulin resistance and obesity-associated ATM polarisation in mice. METHODS: Five-week-old C57/BL6 mice were fed on a low-fat diet or HFD for 20 weeks, with some mice receiving supplementation with 0.01% LU from weeks 1 or 10 of the HFD to assess the actions of LU on insulin resistance and ATM polarisation. Furthermore, the role of LU in metabolic-dysfunction-associated macrophage phenotypes was investigated in vitro. RESULTS: Dietary LU supplementation, either for 20 weeks or from weeks 10 to 20 of an HFD, significantly improved insulin resistance in HFD-fed mice. In addition, inflammatory macrophage infiltration and polarisation were suppressed in mouse epididymal adipose tissues. Furthermore, LU treatment directly reversed lipopolysaccharide-stimulated and metabolism-regulated molecules, and induced inflammatory polarisation in mouse RAW264.7 cells and peritoneal cavity resident macrophages. Finally, using the selective AMP-activated protein kinase (AMPK) inhibitor compound C and Ampkα1 (also known as Prkaa1) silencing with siRNA, we found that LU activated AMPKα1 in macrophages to inhibit their inflammatory polarisation and enhanced insulin signals in adipocytes that were stimulated with macrophage-conditioned media. CONCLUSIONS/INTERPRETATION: Dietary LU ameliorated insulin resistance in diet-induced obese mice by promoting AMPKα1 signalling in ATMs.